Typical as well as atypical neuroleptics increase radical formation in rat brain areas. Studies in-vitro and in-vivo

Typical and atypical neuroleptics show extrapyramidal side effects such as tardive dyskinesia, which can be related to oxidative stress. The aim of our study was, to compare radical formation induced by typical and atypical neuroleptics as compared to well known neurotoxins. In contrast to other radical scavengers the scavenger 1-hydroxy–3-methoxycarbonyl–2,2,5,5-tetramethylpyrrolidine (CMH) can be used both in vitro and in vivo. Superoxide, hydroxycal radicals, and peroxynitrite transforme CMH to CM, which can easily detected by ESR spectroscopy. In vitro, homogenate of different rat brain areas was incubated with haloperidol, olanzapine, or the dopaminergic neurotoxine in the presence of CMH. In microdialysis-experiments in the hippocampus, CMH was added to the perfusion fluid. The incubation of brain homogenate with haloperidol in all brain areas studied led to marked significant increases of CM. This effect was highest in the striatum. Radical formation induced by olanzapine was lower then for haloperidol in all areas studied. The dopaminergic neurotoxin TaClo showed highest values for CM in all brain areas. In-vivo we could observe a marked radical formation induced by haloperidol in the hippocampus. The presented data strengthen the role of radical formation as cause for exprapyramidal side effects of neuroleptic treatment. Our data show that radical formation is not limited to basal ganglia, and therefore other then dopaminergic neurons might be affected.